Interest of Tumor-Specific CD4 T Helper 1 Cells for Therapeutic Anticancer Vaccine

Jeanne Galaine, Christophe Borg, Yann Godet, Olivier Adotévi, Jeanne Galaine, Christophe Borg, Yann Godet, Olivier Adotévi

Abstract

Nowadays, immunotherapy represents one promising approach for cancer treatment. Recently, spectacular results of cancer immunotherapy clinical trials have confirmed the crucial role of immune system in cancer regression. Therapeutic cancer vaccine represents one widely used immunotherapy strategy to stimulate tumor specific T cell responses but clinical impact remains disappointing in targeting CD8 T cells. Although CD8 T cells have been initially considered to be the main protagonists, it is now clear that CD4 T cells also play a critical role in antitumor response. In this article, we discuss the role of tumor antigen-specific CD4 T cell responses and how we can target these cells to improve cancer vaccines.

Keywords: CD4 T cell; cancer vaccine; helper peptide; tumor antigen.

References

    1. Sharma P., Allison J.P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell. 2015;161:205–214. doi: 10.1016/j.cell.2015.03.030.
    1. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer. 2012;12:252–264. doi: 10.1038/nrc3239.
    1. Chen D.S., Mellman I. Oncology meets immunology: The cancer-immunity cycle. Immunity. 2013;39:1–10. doi: 10.1016/j.immuni.2013.07.012.
    1. Butterfield L.H. Cancer vaccines. Br. Med. J. 2015 doi: 10.1136/bmj.h988.
    1. Ajewski T.F., Meng Y., Harlin H. Immune suppression in the tumor microenvironment. J. Immunother. 2006;29:233–240. doi: 10.1097/01.cji.0000199193.29048.56.
    1. Hunder N.N., Wallen H., Cao J., Hendricks D.W., Reilly J.Z., Rodmyre R., Jungbluth A., Gnjatic S., Thompson J.A., Yee C. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N. Engl. J. Med. 2008;358:2698–2703. doi: 10.1056/NEJMoa0800251.
    1. Tran E., Turcotte S., Gros A., Robbins P.F., Lu Y.C., Dudley M.E., Wunderlich J.R., Somerville R.P., Hogan K., Hinrichs C.S., et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344:641–645. doi: 10.1126/science.1251102.
    1. Slingluff C.L., Lee S., Zhao F., Chianese-Bullock K.A., Olson W.C., Butterfield L.H., Whiteside T.L., Leming P.D., Kirkwood J.M. A randomized phase II trial of multiepitope vaccination with melanoma peptides for cytotoxic T cells and helper T cells for patients with metastatic melanoma (E1602) Clin. Cancer Res. 2013;19:4228–4238. doi: 10.1158/1078-0432.CCR-13-0002.
    1. Reed C.M., Cresce N.D., Mauldin I.S., Slingluff C.L., Olson W.C. Vaccination with melanoma helper peptides induces antibody responses associated with improved overall survival. Clin. Cancer Res. 2015 doi: 10.1158/1078-0432.CCR-15-0233.
    1. Kreiter S., Vormehr M., van de Roemer N., Diken M., Löwer M., Diekmann J., Boegel S., Schrörs B., Vascotto F., Castle J.C., et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520:692–696. doi: 10.1038/nature14426.
    1. Zanetti M. Tapping CD4 T Cells for Cancer Immunotherapy: The Choice of Personalized Genomics. J. Immunol. 2015;194:2049–2056. doi: 10.4049/jimmunol.1402669.
    1. Mosmann T.R., Coffman R.L. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045.
    1. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 2005;6:345–352. doi: 10.1038/ni1178.
    1. Korn T., Oukka M., Kuchroo V., Bettelli E. Th17 cells: Effector T cells with inflammatory properties. Semin. Immunol. 2007;19:362–371. doi: 10.1016/j.smim.2007.10.007.
    1. Végran F., Apetoh L., Ghiringhelli F. Th9 cells: A novel CD4 T-cell subset in the immune war against cancer. Cancer Res. 2015;75:475–479. doi: 10.1158/0008-5472.CAN-14-2748.
    1. Trifari S., Kaplan C.D., Tran E.H., Crellin N.K., Spits H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells. Nat. Immunol. 2009;10:864–871. doi: 10.1038/ni.1770.
    1. Crotty S. Follicular helper CD4 T cells (TFH) Annu. Rev. Immunol. 2011;29:621–663. doi: 10.1146/annurev-immunol-031210-101400.
    1. Geginat J., Paroni M., Maglie S., Alfen J.S., Kastirr I., Gruarin P., de Simone M., Pagani M., Abrignani S. Plasticity of human CD4 T cell subsets. Front. Immunol. 2014 doi: 10.3389/fimmu.2014.00630.
    1. Zhu J., Paul W.E. CD4 T cells: Fates, functions, and faults. Blood. 2008;112:1557–1569. doi: 10.1182/blood-2008-05-078154.
    1. Kennedy R., Celis E. Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunol. Rev. 2008;222:129–144. doi: 10.1111/j.1600-065X.2008.00616.x.
    1. Kim H.J., Cantor H. CD4 T-cell subsets and tumor immunity: The helpful and the not-so-helpful. Cancer Immunol. Res. 2014;2:91–98. doi: 10.1158/2326-6066.CIR-13-0216.
    1. Pardoll D.M., Topalian S.L. The role of CD4+ T cell responses in antitumor immunity. Curr. Opin. Immunol. 1998;10:588–594. doi: 10.1016/S0952-7915(98)80228-8.
    1. Ridge J.P., di Rosa F., Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature. 1998;393:474–478. doi: 10.1038/30989.
    1. Bennett S.R., Carbone F.R., Karamalis F., Flavell R.A., Miller J.F., Heath W.R. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature. 1998;393:478–480.
    1. Smith C.M., Wilson N.S., Waithman J., Villadangos J.A., Carbone F.R., Heath W.R., Belz G.T. Cognate CD4+ T cell licensing of dendritic cells in CD8+ T cell immunity. Nat. Immunol. 2004;5:1143–1148. doi: 10.1038/ni1129.
    1. Wong S.B.J., Bos R., Sherman L.A. Tumor-specific CD4+ T cells render the tumor environment permissive for infiltration by low-avidity CD8+ T cells. J. Immunol. 2008;180:3122–3131. doi: 10.4049/jimmunol.180.5.3122.
    1. Bos R., Sherman L.A. CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res. 2010;70:8368–8377. doi: 10.1158/0008-5472.CAN-10-1322.
    1. Dosset M., Godet Y., Vauchy C., Beziaud L., Lone Y.C., Sedlik C., Liard C., Levionnois E., Clerc B., Sandoval F., et al. Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor. Clin. Cancer Res. 2012;18:6284–6295. doi: 10.1158/1078-0432.CCR-12-0896.
    1. Dosset M., Vauchy C., Beziaud L., Adotevi O., Godet Y. Universal tumor-reactive helper peptides from telomerase as new tools for anticancer vaccination. Oncoimmunology. 2013 doi: 10.4161/onci.23430.
    1. Nakanishi Y., Lu B., Gerard C., Iwasaki A. CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature. 2009;462:510–513. doi: 10.1038/nature08511.
    1. Ikeda H., Old L.J., Schreiber R.D. The roles of IFNγ in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002;13:95–109. doi: 10.1016/S1359-6101(01)00038-7.
    1. Xie Y., Akpinarli A., Maris C., Hipkiss E.L., Lane M., Kwon E.K.M., Muranski P., Restifo N.P., Antony P.A. Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanoma. J. Exp. Med. 2010;207:651–667. doi: 10.1084/jem.20091921.
    1. Quezada S.A., Simpson T.R., Peggs K.S., Merghoub T., Vider J., Fan X., Blasberg R., Yagita H., Muranski P., Antony P.A., et al. Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med. 2010;207:637–650. doi: 10.1084/jem.20091918.
    1. Matsuzaki J., Tsuji T., Luescher I., Old L.J., Shrikant P., Gnjatic S., Odunsi K. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4+ T Cells. Cancer Immunol. Res. 2014;2:341–350. doi: 10.1158/2326-6066.CIR-13-0138.
    1. Ayyoub M., Pignon P., Classe J.-M., Odunsi K., Valmori D. CD4+ T effectors specific for the tumor antigen NY-ESO-1 are highly enriched at ovarian cancer sites and coexist with, but are distinct from, tumor-associated Treg. Cancer Immunol. Res. 2013;1:303–308. doi: 10.1158/2326-6066.CIR-13-0062-T.
    1. Campi G., Crosti M., Consogno G., Facchinetti V., Conti-Fine B.M., Longhi R., Casorati G., Dellabona P., Protti M.P. CD4+ T cells from healthy subjects and colon cancer patients recognize a carcinoembryonic antigen-specific immunodominant epitope. Cancer Res. 2003;63:8481–8486.
    1. Godet Y., Fabre E., Dosset M., Lamuraglia M., Levionnois E., Ravel P., Benhamouda N., Cazes A., le Pimpec-Barthes F., Gaugler B., et al. Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: Potential synergistic effect with chemotherapy response. Clin. Cancer Res. 2012;18:2943–2953. doi: 10.1158/1078-0432.CCR-11-3185.
    1. Vauchy C., Gamonet C., Ferrand C., Daguindau E., Galaine J., Beziaud L., Chauchet A., Henry Dunand C.J., Deschamps M., Rohrlich P.S., et al. CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes. Int. J. Cancer. 2015;137:116–126. doi: 10.1002/ijc.29366.
    1. Wang X.F., Kerzerho J., Adotevi O., Nuyttens H., Badoual C., Munier G., Oudard S., Tu S., Tartour E., Maillère B. Comprehensive analysis of HLA-DR- and HLA-DP4-restricted CD4+ T cell response specific for the tumor-shared antigen survivin in healthy donors and cancer patients. J. Immunol. 2008;181:431–439. doi: 10.4049/jimmunol.181.1.431.
    1. Kudela P., Sun Z., Fourcade J., Janjic B., Kirkwood J.M., Maillere B., Zarour H.M. Epitope hierarchy of spontaneous CD4+ T cell responses to LAGE-1. J. Immunol. 2011;186:312–322. doi: 10.4049/jimmunol.1001989.
    1. Ohue Y., Eikawa S., Okazaki N., Mizote Y., Isobe M., Uenaka A., Fukuda M., Old L.J., Oka M., Nakayama E. Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients. Int. J. Cancer. 2012;131:E649–E658. doi: 10.1002/ijc.27359.
    1. Tsuji T., Matsuzaki J., Ritter E., Miliotto A., Ritter G., Odunsi K., Old L.J., Gnjatic S. Split T cell tolerance against a self/tumor antigen: Spontaneous CD4+ but not CD8+ T cell responses against p53 in cancer patients and healthy donors. PLoS ONE. 2011;6:e23651. doi: 10.1371/journal.pone.0023651.
    1. Yoshida N., Abe H., Ohkuri T., Wakita D., Sato M., Noguchi D., Miyamoto M., Morikawa T., Kondo S., Ikeda H., et al. Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell infiltration in non-small cell lung carcinoma and their prognostic significance. Int. J. Oncol. 2006;28:1089–1098. doi: 10.3892/ijo.28.5.1089.
    1. Zhang Z., Huang J., Zhang C., Yang H., Qiu H., Li J., Liu Y., Qin L., Wang L., Hao S., et al. Infiltration of dendritic cells and T lymphocytes predicts favorable outcome in epithelial ovarian cancer. Cancer Gene Ther. 2015;22:198–206. doi: 10.1038/cgt.2015.7.
    1. Fridman W.H., Dieu-Nosjean M.C., Pagès F., Cremer I., Damotte D., Sautès-Fridman C., Galon J. The immune microenvironment of human tumors: General significance and clinical impact. Cancer Microenviron. 2013;6:117–122. doi: 10.1007/s12307-012-0124-9.
    1. Fridman W.H., Pagès F., Sautès-Fridman C., Galon J. The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer. 2012;12:298–306. doi: 10.1038/nrc3245.
    1. Fayolle C., Deriaud E., Leclerc C. In vivo induction of cytotoxic T cell response by a free synthetic peptide requires CD4+ T cell help. J. Immunol. 1991;147:4069–4073.
    1. Antony P.A., Piccirillo C.A., Akpinarli A., Finkelstein S.E., Speiss P.J., Surman D.R., Palmer D.C., Chan C.C., Klebanoff C.A., Overwijk W.W., et al. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J. Immunol. 2005;174:2591–2601. doi: 10.4049/jimmunol.174.5.2591.
    1. Knutson K.L., Disis M.L. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol. Immunother. 2005;54:721–728. doi: 10.1007/s00262-004-0653-2.
    1. Cecil D.L., Holt G.E., Park K.H., Gad E., Rastetter L., Childs J., Higgins D., Disis M.L. Elimination of IL-10-inducing T-helper epitopes from an IGFBP-2 vaccine ensures potent antitumor activity. Cancer Res. 2014;74:2710–2718. doi: 10.1158/0008-5472.CAN-13-3286.
    1. Beatty G.L., Vonderheide R.H. Telomerase as a universal tumor antigen for cancer vaccines. Expert Rev. Vaccines. 2008;7:881–887. doi: 10.1586/14760584.7.7.881.
    1. Kobayashi H., Wood M., Song Y., Appella E., Celis E. Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Res. 2000;60:5228–5236.
    1. Piesche M., Hildebrandt Y., Zettl F., Chapuy B., Schmitz M., Wulf G., Trümper L., Schroers R. Identification of a promiscuous HLA DR-restricted T-cell epitope derived from the inhibitor of apoptosis protein survivin. Hum. Immunol. 2007;68:572–576. doi: 10.1016/j.humimm.2007.03.007.
    1. Jäger E., Jäger D., Karbach J., Chen Y.T., Ritter G., Nagata Y., Gnjatic S., Stockert E., Arand M., Old L.J., et al. Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4 * 0101-0103 and recognized by CD4+ T lymphocytes of patients with NY-ESO-1-expressing melanoma. J. Exp. Med. 2000;191:625–630. doi: 10.1084/jem.191.4.625.
    1. Hiltbold E.M., Ciborowski P., Finn O.J. Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ T cells. Cancer Res. 1998;58:5066–5070.
    1. Kobayashi H., Celis E. Peptide epitope identification for tumor-reactive CD4 T cells. Curr. Opin. Immunol. 2008;20:221–227. doi: 10.1016/j.coi.2008.04.011.
    1. Adotévi O., Dosset M., Galaine J., Beziaud L., Godet Y., Borg C. Targeting antitumor CD4 helper T cells with universal tumor-reactive helper peptides derived from telomerase for cancer vaccine. Hum. Vaccines Immunother. 2013;9:1073–1077. doi: 10.4161/hv.23587.
    1. Del Guercio M.F., Alexander J., Kubo R.T., Arrhenius T., Maewal A., Appella E., Hoffman S.L., Jones T., Valmori D., Sakaguchi K., et al. Potent immunogenic short linear peptide constructs composed of B cell epitopes and Pan DR T helper epitopes (PADRE) for antibody responses in vivo. Vaccine. 1997;15:441–448. doi: 10.1016/S0264-410X(97)00186-2.
    1. Valmori D., Pessi A., Bianchi E., Corradin G. Use of human universally antigenic tetanus toxin T cell epitopes as carriers for human vaccination. J. Immunol. 1992;149:717–721.
    1. Slingluff C.L., Petroni G.R., Chianese-Bullock K.A., Smolkin M.E., Ross M.I., Haas N.B., von Mehren M., Grosh W.W. Randomized multicenter trial of the effects of melanoma-associated helper peptides and cyclophosphamide on the immunogenicity of a multipeptide melanoma vaccine. J. Clin. Oncol. 2011;29:2924–2932. doi: 10.1200/JCO.2010.33.8053.
    1. Woods K., Cebon J. Tumor-specific T-cell help is associated with improved survival in melanoma. Clin. Cancer Res. 2013;19:4021–4023. doi: 10.1158/1078-0432.CCR-13-1349.
    1. Disis M.L., Wallace D.R., Gooley T.A., Dang Y., Slota M., Lu H., Coveler A.L., Childs J.S., Higgins D.M., Fintak P.A., et al. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J. Clin. Oncol. 2009;27:4685–4692. doi: 10.1200/JCO.2008.20.6789.
    1. Brunsvig P.F., Kyte J.A., Kersten C., Sundstrøm S., Møller M., Nyakas M., Hansen G.L., Gaudernack G., Aamdal S. Telomerase peptide vaccination in NSCLC: A phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial. Clin. Cancer Res. 2011;17:6847–6857. doi: 10.1158/1078-0432.CCR-11-1385.
    1. Kyte J.A. Cancer vaccination with telomerase peptide GV1001. Expert Opin. Investig. Drugs. 2009;18:687–694. doi: 10.1517/13543780902897631.
    1. Middleton G., Silcocks P., Cox T., Valle J., Wadsley J., Propper D., Coxon F., Ross P., Madhusudan S., Roques T., et al. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): An open-label, randomised, phase 3 trial. Lancet Oncol. 2014;15:829–840. doi: 10.1016/S1470-2045(14)70236-0.
    1. Widmann C., Romero P., Maryanski J.L., Corradin G., Valmori D. T helper epitopes enhance the cytotoxic response of mice immunized with MHC class I-restricted malaria peptides. J. Immunol. Methods. 1992;155:95–99. doi: 10.1016/0022-1759(92)90275-X.
    1. Shirai M., Pendleton C.D., Ahlers J., Takeshita T., Newman M., Berzofsky J.A. Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8+ CTL in vivo with peptide vaccine constructs. J. Immunol. 1994;152:549–556.
    1. Hiranuma K., Tamaki S., Nishimura Y., Kusuki S., Isogawa M., Kim G., Kaito M., Kuribayashi K., Adachi Y., Yasutomi Y. Helper T cell determinant peptide contributes to induction of cellular immune responses by peptide vaccines against hepatitis C virus. J. Gen. Virol. 1999;80:187–193.
    1. Bijker M.S., van den Eeden S.J.F., Franken K.L., Melief C.J.M., van der Burg S.H., Offringa R. Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation. Eur. J. Immunol. 2008;38:1033–1042. doi: 10.1002/eji.200737995.
    1. Zeng G., Li Y., El-Gamil M., Sidney J., Sette A., Wang R., Rosenberg S.A., Robbins P.F. Generation of NY-ESO-1-specific CD4+ and CD8+ T cells by a single peptide with dual MHC class I and class II specificities: A new strategy for vaccine design. Cancer Res. 2002;62:3630–3635.
    1. Van der Burg S.H., Melief C.J. Therapeutic vaccination against human papilloma virus induced malignancies. Curr. Opin. Immunol. 2011;23:252–257. doi: 10.1016/j.coi.2010.12.010.
    1. Zwaveling S., Mota S.C.F., Nouta J., Johnson M., Lipford G.B., Offringa R., Burg S.H., van der Melief C.J.M. Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J. Immunol. 2002;169:350–358. doi: 10.4049/jimmunol.169.1.350.
    1. Vambutas A., DeVoti J., Nouri M., Drijfhout J.W., Lipford G.B., Bonagura V.R., van der Burg S.H., Melief C.J.M. Therapeutic vaccination with papillomavirus E6 and E7 long peptides results in the control of both established virus-induced lesions and latently infected sites in a pre-clinical cottontail rabbit papillomavirus model. Vaccine. 2005;23:5271–5280. doi: 10.1016/j.vaccine.2005.04.049.
    1. Kenter G.G., Welters M.J.P., Valentijn A.R.P.M., Lowik M.J.G., Berends-van der Meer D.M.A., Vloon A.P.G., Essahsah F., Fathers L.M., Offringa R., Drijfhout J.W., et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N. Engl. J. Med. 2009;361:1838–1847. doi: 10.1056/NEJMoa0810097.
    1. Disis M.L., Gooley T.A., Rinn K., Davis D., Piepkorn M., Cheever M.A., Knutson K.L., Schiffman K. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J. Clin. Oncol. 2002;20:2624–2632. doi: 10.1200/JCO.2002.06.171.
    1. Aarntzen E.H.J.G., de Vries I.J.M., Lesterhuis W.J., Schuurhuis D., Jacobs J.F.M., Bol K., Schreibelt G., Mus R., de Wilt J.H.W., Haanen J.B.A.G., et al. Targeting CD4+ T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination. Cancer Res. 2013;73:19–29. doi: 10.1158/0008-5472.CAN-12-1127.
    1. Wierecky J., Müller M.R., Wirths S., Halder-Oehler E., Dörfel D., Schmidt S.M., Häntschel M., Brugger W., Schröder S., Horger M.S., et al. Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res. 2006;66:5910–5918. doi: 10.1158/0008-5472.CAN-05-3905.
    1. Inderberg-Suso E.M., Trachsel S., Lislerud K., Rasmussen A.M., Gaudernack G. Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001. OncoImmunology. 2012;1:670–686. doi: 10.4161/onci.20426.
    1. Hu Y., Petroni G.R., Olson W.C., Czarkowski A., Smolkin M.E., Grosh W.W., Chianese-Bullock K.A., Slingluff C.L. Immunologic hierarchy, class II MHC promiscuity, and epitope spreading of a melanoma helper peptide vaccine. Cancer Immunol. Immunother. 2014;63:779–786. doi: 10.1007/s00262-014-1551-x.
    1. Protti M.P., Monte L.D., Lullo G.D. Tumor antigen-specific CD4+ T cells in cancer immunity: From antigen identification to tumor prognosis and development of therapeutic strategies. Tissue Antigens. 2014;83:237–246. doi: 10.1111/tan.12329.
    1. Simon T., Fonteneau J.F., Grégoire M. Requirement of tumor-associated antigen-specific CD4+ T cells for an efficient dendritic cell vaccine in antitumor immunotherapy. Immunotherapy. 2013;5:565–567. doi: 10.2217/imt.13.45.
    1. Grabowska A.K., Kaufmann A.M., Riemer A.B. Identification of promiscuous HPV16-derived T helper cell epitopes for therapeutic HPV vaccine design. Int. J. Cancer. 2015;136:212–224. doi: 10.1002/ijc.28968.
    1. Andersen R.S., Thrue C.A., Junker N., Lyngaa R., Donia M., Ellebæk E., Svane I.M., Schumacher T.N., Thor Straten P., Hadrup S.R. Dissection of T-cell antigen specificity in human melanoma. Cancer Res. 2012;72:1642–1650. doi: 10.1158/0008-5472.CAN-11-2614.
    1. Benlalam H., Labarrière N., Linard B., Derré L., Diez E., Pandolfino M.C., Bonneville M., Jotereau F. Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): Implications for immunotherapy. Eur. J. Immunol. 2001;31:2007–2015. doi: 10.1002/1521-4141(200107)31:7<2007::AID-IMMU2007>;2-S.
    1. Lennerz V., Fatho M., Gentilini C., Frye R.A., Lifke A., Ferel D., Wölfel C., Huber C., Wölfel T. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc. Natl. Acad. Sci. USA. 2005;102:16013–16018. doi: 10.1073/pnas.0500090102.
    1. Danan-Gotthold M., Golan-Gerstl R., Eisenberg E., Meir K., Karni R., Levanon E.Y. Identification of recurrent regulated alternative splicing events across human solid tumors. Nucleic Acids Res. 2015 doi: 10.1093/nar/gkv210.
    1. Guilloux Y., Lucas S., Brichard V.G., Van Pel A., Viret C., de Plaen E., Brasseur F., Lethé B., Jotereau F., Boon T. A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N-acetylglucosaminyl transferase V gene. J. Exp. Med. 1996;183:1173–1183. doi: 10.1084/jem.183.3.1173.
    1. Nehrt N.L., Peterson T.A., Park D., Kann M.G. Domain landscapes of somatic mutations in cancer. BMC Genomics. 2012 doi: 10.1186/1471-2164-13-S4-S9.
    1. Yadav M., Jhunjhunwala S., Phung Q.T., Lupardus P., Tanguay J., Bumbaca S., Franci C., Cheung T.K., Fritsche J., Weinschenk T., et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515:572–576. doi: 10.1038/nature14001.
    1. Linnemann C., van Buuren M.M., Bies L., Verdegaal E.M.E., Schotte R., Calis J.J.A., Behjati S., Velds A., Hilkmann H., Atmioui D.E., et al. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nat. Med. 2015;21:81–85. doi: 10.1038/nm.3773.
    1. Schumacher T.N., Schreiber R.D. Neoantigens in cancer immunotherapy. Science. 2015;348:69–74. doi: 10.1126/science.aaa4971.
    1. Snyder A., Makarov V., Merghoub T., Yuan J., Zaretsky J.M., Desrichard A., Walsh L.A., Postow M.A., Wong P., Ho T.S., et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 2014;371:2189–2199. doi: 10.1056/NEJMoa1406498.
    1. Rizvi N.A., Hellmann M.D., Snyder A., Kvistborg P., Makarov V., Havel J.J., Lee W., Yuan J., Wong P., Ho T.S., et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128. doi: 10.1126/science.aaa1348.
    1. Paul S., Lindestam Arlehamn C.S., Scriba T.J., Dillon M.B.C., Oseroff C., Hinz D., McKinney D.M., Carrasco Pro S., Sidney J., Peters B., et al. Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes. J. Immunol. Methods. 2015 doi: 10.1016/j.jim.2015.03.022.
    1. Ding L., Ellis M.J., Li S., Larson D.E., Chen K., Wallis J.W., Harris C.C., McLellan M.D., Fulton R.S., Fulton L.L., et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010;464:999–1005. doi: 10.1038/nature08989.
    1. Marusyk A., Almendro V., Polyak K. Intra-tumour heterogeneity: A looking glass for cancer? Nat. Rev. Cancer. 2012;12:323–334. doi: 10.1038/nrc3261.
    1. Linette G.P., Stadtmauer E.A., Maus M.V., Rapoport A.P., Levine B.L., Emery L., Litzky L., Bagg A., Carreno B.M., Cimino P.J., et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013;122:863–871. doi: 10.1182/blood-2013-03-490565.
    1. Tumeh P.C., Harview C.L., Yearley J.H., Shintaku I.P., Taylor E.J.M., Robert L., Chmielowski B., Spasic M., Henry G., Ciobanu V., et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–571. doi: 10.1038/nature13954.
    1. Walter S., Weinschenk T., Stenzl A., Zdrojowy R., Pluzanska A., Szczylik C., Staehler M., Brugger W., Dietrich P.Y., Mendrzyk R., et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat. Med. 2012;18:1254–1261. doi: 10.1038/nm.2883.
    1. Apetoh L., Ladoire S., Coukos G., Ghiringhelli F. Combining immunotherapy and anticancer agents: The right path to achieve cancer cure? Ann. Oncol. 2015 doi: 10.1093/annonc/mdv209.
    1. Farsaci B., Donahue R.N., Coplin M.A., Grenga I., Lepone L.M., Molinolo A.A., Hodge J.W. Immune consequences of decreasing tumor vasculature with antiangiogenic tyrosine kinase inhibitors in combination with therapeutic vaccines. Cancer Immunol. Res. 2014;2:1090–1102. doi: 10.1158/2326-6066.CIR-14-0076.
    1. Gibney G.T., Kudchadkar R.R., DeConti R.C., Thebeau M.S., Czupryn M.P., Tetteh L., Eysmans C., Richards A., Schell M.J., Fisher K.J., et al. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin. Cancer Res. 2015;21:712–720. doi: 10.1158/1078-0432.CCR-14-2468.
    1. Sawada Y., Yoshikawa T., Shimomura M., Iwama T., Endo I., Nakatsura T. Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes. Int. J. Oncol. 2015;46:28–36. doi: 10.3892/ijo.2014.2737.

Source: PubMed

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